A major aim of the experiments outlined in this proposal is to determine the enzymatic mechanisms responsible for the biosynthesis of O-alkyl and O-alk-l-enyl ether moieties in glycerolipids of cancer cells. In addition we plan to investigate specific inhibitors of key enzymes in the pathway of ether lipids and to determine their ability to inhibit malignant transformation. Substrate analogs that are incorporated into biomembranes will be studied from the point of view of how they alter enzymatic and transport properties of the membrane. The properties of NADPH:acyl-CoA oxidoreductase (forms the fatty alcohols that are precursors of the ether chains) and its role as a regulatory enzyme will be determined in cells that are transformed by SV40 sarcoma viruses or 3-methylcholanthrene. These studies will be done with enzyme preparations from a number of primary animal tumors induced by chemicals and viruses, transplantable tumors in mice and rats, and several types of animal cells that can be transformed in tissue culture.